MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer

Summary: Activation of mitogenic signaling pathways is a common oncogenic driver of many solid tumors including lung cancer. Although activating mutations in the mitogen-activated protein kinase (MAPK) pathway are prevalent in non-small cell lung cancers, MAPK pathway activity, counterintuitively, i...

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Autores principales:	Rebecca Caeser, Christopher Hulton, Emily Costa, Vidushi Durani, Megan Little, Xiaoping Chen, Sam E. Tischfield, Marina Asher, Faruk Erdem Kombak, Shweta S. Chavan, Nisargbhai S. Shah, Metamia Ciampricotti, Elisa de Stanchina, John T. Poirier, Charles M. Rudin, Triparna Sen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Cell biology Molecular biology Science Q
Acceso en línea:	https://doaj.org/article/408084487e324b9abf64eba52e8ffc2a
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spelling	oai:doaj.org-article:408084487e324b9abf64eba52e8ffc2a2021-11-20T05:08:29ZMAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer2589-004210.1016/j.isci.2021.103224https://doaj.org/article/408084487e324b9abf64eba52e8ffc2a2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221011925https://doaj.org/toc/2589-0042Summary: Activation of mitogenic signaling pathways is a common oncogenic driver of many solid tumors including lung cancer. Although activating mutations in the mitogen-activated protein kinase (MAPK) pathway are prevalent in non-small cell lung cancers, MAPK pathway activity, counterintuitively, is relatively suppressed in the more aggressively proliferative small cell lung cancer (SCLC). Here, we elucidate the role of the MAPK pathway and how it interacts with other signaling pathways in SCLC. We find that the most common SCLC subtype, SCLC-A associated with high expression of ASCL1, is selectively sensitive to MAPK activation in vitro and in vivo through induction of cell-cycle arrest and senescence. We show strong upregulation of ERK negative feedback regulators and STAT signaling upon MAPK activation in SCLC-A lines. These findings provide insight into the complexity of signaling networks in SCLC and suggest subtype-specific mitogenic vulnerabilities.Rebecca CaeserChristopher HultonEmily CostaVidushi DuraniMegan LittleXiaoping ChenSam E. TischfieldMarina AsherFaruk Erdem KombakShweta S. ChavanNisargbhai S. ShahMetamia CiampricottiElisa de StanchinaJohn T. PoirierCharles M. RudinTriparna SenElsevierarticleBiological sciencesCell biologyMolecular biologyScienceQENiScience, Vol 24, Iss 11, Pp 103224- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Cell biology Molecular biology Science Q
spellingShingle	Biological sciences Cell biology Molecular biology Science Q Rebecca Caeser Christopher Hulton Emily Costa Vidushi Durani Megan Little Xiaoping Chen Sam E. Tischfield Marina Asher Faruk Erdem Kombak Shweta S. Chavan Nisargbhai S. Shah Metamia Ciampricotti Elisa de Stanchina John T. Poirier Charles M. Rudin Triparna Sen MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer
description	Summary: Activation of mitogenic signaling pathways is a common oncogenic driver of many solid tumors including lung cancer. Although activating mutations in the mitogen-activated protein kinase (MAPK) pathway are prevalent in non-small cell lung cancers, MAPK pathway activity, counterintuitively, is relatively suppressed in the more aggressively proliferative small cell lung cancer (SCLC). Here, we elucidate the role of the MAPK pathway and how it interacts with other signaling pathways in SCLC. We find that the most common SCLC subtype, SCLC-A associated with high expression of ASCL1, is selectively sensitive to MAPK activation in vitro and in vivo through induction of cell-cycle arrest and senescence. We show strong upregulation of ERK negative feedback regulators and STAT signaling upon MAPK activation in SCLC-A lines. These findings provide insight into the complexity of signaling networks in SCLC and suggest subtype-specific mitogenic vulnerabilities.
format	article
author	Rebecca Caeser Christopher Hulton Emily Costa Vidushi Durani Megan Little Xiaoping Chen Sam E. Tischfield Marina Asher Faruk Erdem Kombak Shweta S. Chavan Nisargbhai S. Shah Metamia Ciampricotti Elisa de Stanchina John T. Poirier Charles M. Rudin Triparna Sen
author_facet	Rebecca Caeser Christopher Hulton Emily Costa Vidushi Durani Megan Little Xiaoping Chen Sam E. Tischfield Marina Asher Faruk Erdem Kombak Shweta S. Chavan Nisargbhai S. Shah Metamia Ciampricotti Elisa de Stanchina John T. Poirier Charles M. Rudin Triparna Sen
author_sort	Rebecca Caeser
title	MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer
title_short	MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer
title_full	MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer
title_fullStr	MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer
title_full_unstemmed	MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer
title_sort	mapk pathway activation selectively inhibits ascl1-driven small cell lung cancer
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/408084487e324b9abf64eba52e8ffc2a
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_version_	1718419536942727168

MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer

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